graduate student
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
City clinical oncology dispensary
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Sankt - Peterburg, St. Petersburg, Russian Federation
UDK 61 Медицина. Охрана здоровья
GRNTI 76.29 Клиническая медицина
OKSO 31.08.74 Стоматология хирургическая
BBK 528 Фармакология. Фармация. Токсикология
BBK 566 Стоматология
BISAC MED016050 Dentistry / Oral Surgery
Importance. Determining the influence of different medications in the development of different diseases is a prerequisite for adequate comprehensive treatment of patients. At present, there is insufficient data on the influence of anti-osteoclastic drugs on the microcirculation, which may have an impact. The aim. To study the effects of the monoclonal antibody denosumab on the development of osteonecrosis of the jaw of rats. Methodology. The study was carried out on 36 Wistar Line rats in the Department of Pathophysiology with the course of clinical pathophysiology First Pavlov State Medical University. The osteonecrorosis of the jaws of rats was induced by the extracted of a lower first molar. The observation was carried out with diagnostic studies of microcirculation (doppler), bone structure (3D computer tomography of jaws), followed by statistical processing of the data. Results. It has been shown that the greatest decrease in blood flow rate and the greatest bone defect is determined in the group of rats with the maximum dose of the monoclonal antibody preparation of denosumab by the time of 4 weeks, 0.5 mg/kg intravenous administration. Also, there has been evidence of a difference in blood flow reduction between the histological layers of the lower jaw. Thus, the intrabone blood flow was damaged much more, than the layer of mucous membrane of the gum. Conclusions. The combined method of dopplerography allows the determination of blood flow status on different histological layers. It is possible to determine the extent to which different pharmacological preparations influence the rate of blood flow in the local area without invasive interventions. The study of monoclonal antibodies is an acute problem in the world of surgical dental practice, which requires further study.
Medication-related osteonecrosis of the jaw, denosumab, monoclonal antibodies, combined doppler
1. Aljohani S., Gaudin R., Weiser J., Tröltzsch M., Ehrenfeld M., Kaeppler G., Smeets R., Otto S. Osteonecrosis of the jaw in patients treated with denosumab: A multicenter case series // J Craniomaxillofac Surg. – 2018;46(9):1515-1525. https://doi.org/10.1016/j.jcms.2018.05.046
2. McDonald M.M., Kim A.S., Mulholland B.S., Rauner M. New Insights Into Osteoclast Biology // JBMR Plus. – 2021;30;5(9):e10539. https://doi.org/10.1002/jbm4.10539
3. Bone H.G., Wagman R.B., Brandi M.L., Brown J.P., Chapurlat R., Cummings S.R., Czerwiński E., Fahrleitner-Pammer A., Kendler D.L., Lippuner K., Reginster J.Y., Roux C., Malouf J., Bradley M.N., Daizadeh N.S., Wang A., Dakin P., Pannacciulli N., Dempster D.W., Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension // Lancet Diabetes Endocrinol. – 2017;5(7):513-523. https://doi.org/10.1016/S2213-8587(17)30138-9
4. Migliorini F., Maffulli N., Colarossi G., Eschweiler J., Tingart M., Betsch M. Effect of drugs on bone mineral density in postmenopausal osteoporosis: a Bayesian network meta-analysis // J Orthop Surg Res. – 2021;27;16(1):533. https://doi.org/10.1186/s13018-021-02678-x.
5. Egloff-Juras C., Gallois A., Salleron J., Massard V., Dolivet G., Guillet J., Phulpin B. Denosumab-related osteonecrosis of the jaw: A retrospective study // J Oral Pathol Med. – 2018;47(1):66-70.https://doi.org/10.1111/jop.12646.
6. Fassio A., Bertoldo F., Idolazzi L., Viapiana O., Rossini M., Gatti D. Drug-induced osteonecrosis of the jaw: the state of the art // Reumatismo. – 2017;22;69(1):9-15. https://doi.org/10.4081/reumatismo.2017.983
7. Hadaya D., Soundia A., Gkouveris I. et al. Antiresorptive-Type and Discontinuation-Timing Affect ONJ Burden // Journal of Dental Research. – 2021;100(7):746-753. https://doi.org/10.1177/0022034520986804
8. Hoefert S., Yuan A., Munz A., Grimm M., Elayouti A., Reinert S. Clinical course and therapeutic outcomes of operatively and non-operatively managed patients with denosumab-related osteonecrosis of the jaw (DRONJ) //J Craniomaxillofac Surg. – 2017;45(4):570-578.https://doi.org/10.1016/j.jcms.2017.01.013.
9. Khan A., Morrison A., Cheung A., Hashem W., Compston J. Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015 // Osteoporos Int. – 2016;27(3):853-859. https://doi.org/10.1007/s00198-015-3335-3
10. Lorusso L., Pieruzzi L., Gabriele M., Nisi M., Viola D., Molinaro E., Bottici V., Elisei R., Agate L. Osteonecrosis of the jaw: a rare but possible side effect in thyroid cancer patients treated with tyrosine-kinase inhibitors and bisphosphonates // J Endocrinol Invest. – 2021;21. https://doi.org/10.1007/s40618-021-01634-0.
11. Kostenuik P.J., Nguyen H.Q., McCabe J., Warmington K.S., Kurahara C., Sun N., Chen C., Li L., Cattley R.C., Van G., Scully S., Elliott R., Grisanti M., Morony S., Tan H.L., Asuncion F., Li X., Ominsky M.S., Stolina M., Dwyer D., Dougall W.C., Hawkins N., Boyle W.J., Simonet W.S., Sullivan J.K. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL // J Bone Miner Res. – 2009;24(2):182-195. doi: 10.1359/jbmr.081112. PMID: 19016581
12. Kanis J.A., Cooper C., Rizzoli R., Reginster J.Y. Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women // Osteoporos Int. – 2019;30(1):3-44. https://doi.org/10.1007/s00198-018-4704-5.
13. Lenasi H., Potočnik N., Petrishchev N., Papp M., Egorkina A., Girina M., Skedina M., Kovaleva A. The measurement of cutaneous blood flow in healthy volunteers subjected to physical exercise with ultrasound Doppler imaging and laser Doppler flowmetry // Clin Hemorheol Microcirc. – 2017;65(4):373-381. doi: 10.3233/CH-16204. PMID: 27983546.
14. Alsalih A., Dam A., Lindberg P., Truedsson A. Medication-Related Osteonecrosis of the Jaws Initiated by Zoledronic Acid and Potential Pathophysiology // Dent J (Basel). – 2021;30;9(8):85. https://doi.org/10.3390/dj9080085.
15. Akther F., Razan M.R., Shaligram S., Graham J.L., Stanhope K.L., Allen K.N., Vázquez-Medina J.P., Havel P.J., Rahimian R. Potentiation of Acetylcholine-Induced Relaxation of Aorta in Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Sex-Specific Responses // Front Physiol. – 2021;22;12:616317.https://doi.org/10.3389/fphys.2021.616317
16. Querrer R., Ferrare N., Melo N., Stefani C.M., Dos Reis P.E.D., Mesquita C.R.M., Borges G.A., Leite A.F., Figueiredo P.T. Differences between bisphosphonate-related and denosumab-related osteonecrosis of the jaws: a systematic review // Support Care Cancer. – 2021;29(6):2811-2820. https://doi.org/10.1007/s00520-020-05855-6
17. Eleutherakis-Papaiakovou E., Bamias A. Antiresorptive treatment-associated ONJ // Eur J Cancer Care (Engl). – 2017;26(6). https://doi.org/10.1111/ecc.12787.
18. Loyson T., Van Cann T., Schöffski P., Clement P.M., Bechter O., Spriet I., Coropciuc R., Politis C., Vandeweyer R.O., Schoenaers J., Dumez H., Berteloot P., Neven P., Nackaerts K., Woei-A-Jin F.J.S.H., Punie K., Wildiers H., Beuselinck B. Incidence of osteonecrosis of the jaw in patients with bone metastases treated sequentially with bisphosphonates and denosumab // Acta Clin Belg. – 2018;73(2):100-109. https://doi.org/10.1080/17843286.2017.1348001.
19. Thanakun S., Pornprasertsuk-Damrongsri S., Na Mahasarakham C.P., Techatanawat S., Izumi Y. Increased Plasma Osteocalcin, Oral Disease, and Altered Mandibular Bone Density in Postmenopausal Women // Int J Dent. – 2019;24;2019:3715127. https://doi.org/10.1155/2019/3715127.
20. Rugani P., Walter C., Kirnbauer B., Acham S., Begus-Nahrman Y., Jakse N. Prevalence of Medication-Related Osteonecrosis of the Jaw in Patients with Breast Cancer, Prostate Cancer, and Multiple Myeloma // Dent J (Basel). – 2016;27;4(4):32. https://doi.org/10.3390/dj4040032.
21. Chen J., Chen Q., Hu B., Wang Y., Song J. Effectiveness of alendronate as an adjunct to scaling and root planing in the treatment of periodontitis: a meta-analysis of randomized controlled clinical trials // J Periodontal Implant Sci. – 2016;46(6):382-395. https://doi.org/10.5051/jpis.2016.46.6.382.
22. Williams D.W., Lee C., Kim T. et al. Impaired bone resorption and woven bone formation are associated with development of osteonecrosis of the jaw-like lesions by bisphosphonate and anti-receptor activator of NF-κb ligand antibody in mice // Am J Pathol. – 2014;184(11):3084-3093. Doi:10.1016/j.ajpath.2014.07.010
